Circulating miRNA-21 and Biomarkers of Inflammation, Fibrosis, and Oxidative Stress in Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study

Abstract

Purpose Chronic inflammation, oxidative stress, and fibrosis are interconnected drivers of complications in type 2 diabetes mellitus (T2DM) and may precede detectable changes in conventional clinical markers. MicroRNA-21 (miR-21) has been implicated in all three pathways, but its associations with representative biomarkers have rarely been examined simultaneously in a single T2DM population. We evaluated correlations between circulating miR-21 and serum tumor necrosis factor receptor-1 (TNFR1), transforming growth factor-beta 1 (TGF-β1), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and explored differences by albuminuria status. Patients and Methods This cross-sectional study was a secondary analysis of clinical data and archived serum from 54 adults with T2DM enrolled in the Bogor Non-Communicable Disease Risk Factor Cohort, Indonesia. Most participants had preserved kidney function (mean eGFR 76.9 ± 15.0 mL/min/1.73m2; 63.0% without albuminuria). Circulating miR-21 was quantified by quantitative real-time PCR; TNFR1, TGF-β1, and 8-OHdG were measured by ELISA. Independent associations were evaluated using multivariable linear regression adjusted for age, sex, BMI, HbA1c, LDL cholesterol, and eGFR. Bootstrap resampling and albuminuria-stratified analyses were performed. Results Log2-transformed miR-21 correlated weakly with log2 TNFR1 (ρ = 0.273, P = 0.046) and remained independently associated with TNFR1 after adjustment (β = 0.061, 95% CI 0.001–0.122, P = 0.048). This borderline association was robust to bootstrap resampling and additional adjustment for diabetes duration and statin use. No independent associations were observed with TGF-β1 or 8-OHdG overall. Exploratory findings showed that miR-21 was associated with TGF-β1 among participants with albuminuria (β = 0.286, P = 0.038), but the interaction was not significant (P = 0.087). Conclusion In this T2DM population with predominantly preserved kidney function, circulating miR-21 was associated with TNFR1, a marker of TNF-α–related inflammatory activity, but not with TGF-β1 or 8-OHdG. These exploratory findings, limited by the small sample, borderline statistical significance, and lack of multiplicity adjustment, require confirmation in larger prospective, multicenter studies.